Antisense modulation of BCL-X expression
AssigneeIsis Pharmaceuticals, Inc.
InventorsC. Frank Bennett, Nicholas M. Dean, Brett P. Monia, Brian J. Nickoloff, QingQing Zhang
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Abstract
Compositions and methods are provided for modulating the expression of bcl-x. Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding bcl-x are preferred. Methods of using these compounds for modulation of bcl-x expression and for treatment of diseases associated with expression of bcl-x are also provided.
Claims35
An antisense compound 8 to 30 nucleotides in length targeted to a nucleic acid molecule encoding a human bcl-x, wherein said antisense compound modulates the expression of human bcl-x, and wherein said antisense compound is an antisense oligonucleotide which comprises at least an 8 nucleobase portion of SEQ ID NO:
- 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 31, 32, 33, 34, 36, 37, 38, 39, or 40.
An antisense compound 8 to 30 nucleotides in length which is targeted to a bcl-x RNA transcript containing a first and second alternative splice site, which, when contacted with the transcript, reduces the relative frequency of splicing at said second splice site such that the ratio of resulting RNA splice products is altered and wherein said antisense compounds is targeted to at least a portion of the RNA region within 20 nucleotides to the 5′ side of said second splice site.
An antisense compound which alters splicing of an RNA encoding human bcl-x, such that the ratio of bcl-xs to bcl-xl is altered, and which is targeted to nucleotides 664 to 698 of SEQ ID NO:1, a nucleic acid encoding human bcl-x.
An antisense oligonucleotide comprising SEQ ID No:33, 34 or 46.
Dependencies are inferred from the claim text.